PMID- 19744266
OWN - NLM
STAT- MEDLINE
DCOM- 20100107
LR  - 20091008
IS  - 1478-3231 (Electronic)
IS  - 1478-3223 (Linking)
VI  - 29
IP  - 10
DP  - 2009 Nov
TI  - Z and Mmalton-1-antitrypsin deficiency-associated hepatocellular carcinoma: a 
      genetic study.
PG  - 1593-6
LID - 10.1111/j.1478-3231.2009.02091.x [doi]
AB  - BACKGROUND: The histological hallmark of alpha-1-antitrypsin deficiency (AATD) is 
      the presence of periodic acid-Schiff diastase (PASD)-resistant positive globules 
      in hepatocytes, with a heterogeneous distribution. It is noteworthy that 
      hepatocellular carcinoma (HCC) arises specifically from the AAT-negative areas 
      but the reason for this remains unclear. AIM: To determine whether the different 
      distribution of AAT globules within neoplastic and non-neoplastic hepatocytes is 
      the result of a self-induced correction of the genetic defect. PATIENTS AND 
      METHODS: Two HCV-positive patients with AATD-associated HCC were studied. One 
      patient harboured a compound heterozygous PiSZ genotype whereas the other showed 
      the rarer PiMMmalton in heterozygosity. In both cases, neoplastic hepatocytes 
      appeared globule devoid, while non-neoplastic hepatocytes showed intracytoplasmic 
      accumulation of PASD-positive globules. Laser-assisted microdissection was used 
      to assess a genotype/phenotype correlation in single liver cells from HCC and 
      from non-neoplastic hepatocytes. RESULTS: Direct sequencing of DNA purified from 
      globule-devoid and globule-filled hepatocytes demonstrated that all liver cells 
      carried the same mutant genetic background. CONCLUSION: Our findings indicate 
      that (i) both variants of HCC arising in AAT deficiency (Z and Mmalton) do not 
      accumulate the mutant protein and (ii) the different phenotypic appearance of 
      hepatocytes is not the result of a retromutation during neoplastic 
      transformation, but other mechanisms should be investigated.
FAU - Francalanci, Paola
AU  - Francalanci P
AD  - Department of Pathology, Bambino Gesu Children's Hospital, Rome, Italy. 
      francalanci@opbg.net
FAU - Santorelli, Filippo M
AU  - Santorelli FM
FAU - Saccani, Simona
AU  - Saccani S
FAU - Bonetti, Maria F
AU  - Bonetti MF
FAU - Medicina, Daniela
AU  - Medicina D
FAU - Coni, Pierpaolo
AU  - Coni P
FAU - Faa, Gavino
AU  - Faa G
FAU - Callea, Francesco
AU  - Callea F
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20090910
PL  - United States
TA  - Liver Int
JT  - Liver international : official journal of the International Association for the 
      Study of the Liver
JID - 101160857
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Carcinoma, Hepatocellular/etiology/*genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Immunohistochemistry
MH  - Liver Neoplasms/etiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - alpha 1-Antitrypsin/analysis/*genetics
MH  - alpha 1-Antitrypsin Deficiency/*complications
EDAT- 2009/09/12 06:00
MHDA- 2010/01/08 06:00
CRDT- 2009/09/12 06:00
PHST- 2009/09/12 06:00 [entrez]
PHST- 2009/09/12 06:00 [pubmed]
PHST- 2010/01/08 06:00 [medline]
AID - LIV2091 [pii]
AID - 10.1111/j.1478-3231.2009.02091.x [doi]
PST - ppublish
SO  - Liver Int. 2009 Nov;29(10):1593-6. doi: 10.1111/j.1478-3231.2009.02091.x. Epub 
      2009 Sep 10.